Phamacology in pregnancy& paediatrics

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Phamacology in pregnancy& paediatrics

  1. 1. Pediatric and Perinatal Pharmacology www.freelivedoctor.com
  2. 2. <ul><li>Pregnancy causes one of the most striking changes in physiology of any normal condition that appears in the human body. Changes in the woman’s body are related to several factors including hormonal influences, the growth of the fetus and her own adaptation to all the changes that are occurring. </li></ul>Pregnancy www.freelivedoctor.com
  3. 3. <ul><ul><li>Increased water retention (7-9Lt). </li></ul></ul><ul><ul><li>Increased extracellular volume (4-6Lt). </li></ul></ul><ul><ul><li>Increased cardiac output. </li></ul></ul><ul><ul><li>Decrease colloidal osmotic pressure. </li></ul></ul><ul><ul><li>Progressive increase of renin thru pregnancy. </li></ul></ul><ul><ul><li>Increase levels of aldosterone. </li></ul></ul><ul><ul><li>Decrease peripheral vascular resistance. </li></ul></ul><ul><ul><li>Gastric acid secretion high in 1 ° and 2 nd Trimesters. </li></ul></ul><ul><ul><li>Decrease gastric emptying. </li></ul></ul><ul><ul><li>Increased absorption. </li></ul></ul><ul><ul><li>Increased intestinal transit times. </li></ul></ul><ul><ul><li>Increase body fat. </li></ul></ul>Changes during pregnancy www.freelivedoctor.com
  4. 4. <ul><li>Dilutional decrease in serum albumin levels. More free drug. </li></ul><ul><li>Decrease concentration of total plasma proteins. More free drug. </li></ul><ul><li>Progesterone stimulates hepatic enzyme systems. Increase clearance and shorter half-life. </li></ul><ul><li>Greater fat and glycogen storage in the liver. </li></ul><ul><li>Increased CO 2 gradient between mother and fetus. </li></ul><ul><li>Renal blood flow and GFR increase early in pregnancy and decrease in late pregnancy. </li></ul>Changes during pregnancy (con’t) www.freelivedoctor.com
  5. 5. <ul><ul><li>To cross the placenta </li></ul></ul><ul><ul><li>vs </li></ul></ul><ul><ul><li>not to cross the placenta </li></ul></ul>GOAL: www.freelivedoctor.com
  6. 6. Drug Therapy in Pregnancy <ul><li>PHARMACOKINETICS </li></ul><ul><li>Factors Affecting Drug Transfer to the Fetus </li></ul><ul><ul><li>I . Physicochemical properties of the drug. </li></ul></ul><ul><ul><li>II. Amount of drug reaching the fetus. </li></ul></ul><ul><ul><li>III. Exposure rate. </li></ul></ul><ul><ul><li>IV. Duration of exposure. </li></ul></ul><ul><ul><li>V. Tissue distribution. </li></ul></ul><ul><ul><li>VI. Developmental stage. </li></ul></ul><ul><ul><li>VII. Co-exposure w/other drugs. </li></ul></ul>www.freelivedoctor.com
  7. 7. I. Physicochemical Properties of the Drug <ul><ul><li>A. Lipid solubility </li></ul></ul><ul><ul><li>B. Degree of ionization </li></ul></ul><ul><ul><li>C. Protein binding </li></ul></ul><ul><ul><li>D. Molecular size </li></ul></ul><ul><ul><li>E. Placental and fetal drug metabolism </li></ul></ul><ul><ul><li>F. Placental transport </li></ul></ul>www.freelivedoctor.com
  8. 8. I. Physicochemical Properties of the Drug <ul><li>A. Lipid Solubility </li></ul><ul><ul><li>Lipophilic drugs tend to cross the placenta readily at rates dependent on their molecular weight, charge characteristics, and concentration in the maternal blood. </li></ul></ul><ul><ul><li>Drugs with low lipid solubility tend to be highly bound to plasma protein. </li></ul></ul><ul><ul><li>Their distribution is affected by placental blood flow. </li></ul></ul><ul><ul><li>i.e. thiopental, nicotine, salicylate </li></ul></ul>www.freelivedoctor.com
  9. 9. I. Physicochemical Properties of the Drug <ul><li>B. Degree of Drug Ionization </li></ul><ul><ul><li>In the blood a weak acid or weak base distributes to all compartments of the body differently, forming an equilibrium between charged and uncharged forms of the drug in each compartment. </li></ul></ul><ul><ul><li>Polar substances cross the placenta more slowly than drugs that are ionized at physiologic pH. </li></ul></ul><ul><ul><li>Impermeability of the placenta to ionized/polar compounds is relative rather than absolute. </li></ul></ul><ul><ul><li>i.e. succinylcholine and tubocurarine (ionized, cross slowly) vs salicylate (small amts of the non-ionized drug cross rapidly because they are highly lipid soluble). </li></ul></ul>www.freelivedoctor.com
  10. 10. I. Physicochemical Properties of the Drug <ul><li>C. Protein binding. </li></ul><ul><ul><li>Affected by lipophilicity and ionization state of drug => lipophilic compounds (anesthetic gases) are not greatly affected by protein binding. </li></ul></ul><ul><ul><li>Low affinity of fetal proteins. </li></ul></ul><ul><ul><li>The protein content in fetal plasma increases with gestational age. </li></ul></ul><ul><ul><li>Fetal albumin levels usually exceed maternal levels at birth. </li></ul></ul><ul><ul><li>i.e. sulfonamides, barbiturates, phenytoin and local anesthetic agents. </li></ul></ul>www.freelivedoctor.com
  11. 11. <ul><li>Two mechanisms protect the fetus from drugs in the maternal circulation: </li></ul><ul><li>1) The placenta, which serves as a semipermeable membrane and as a site of drug metabolism. </li></ul><ul><li>2) Liver metabolism of the drug. </li></ul>www.freelivedoctor.com
  12. 12. <ul><li>Placenta - The placenta is a living tissue that synthesizes a number of peptides, enzymes and hormones. It actively transports molecules to the fetus and carries away wastes. It serves as an effective immunologic barrier and is also a site of metabolism of some drugs. </li></ul>www.freelivedoctor.com
  13. 13. <ul><li>The Placenta </li></ul>Umbilical arteries Umbilical vein Chorionic villus Placental septum Endometrial arteries and veins Intervillus space Chorion Amnion www.freelivedoctor.com
  14. 14. The Maternal-Fetal Unit <ul><li>Maternal transfer </li></ul><ul><li>Antibodies </li></ul><ul><li>Drugs </li></ul><ul><li>Hormones </li></ul><ul><li>Nutrients </li></ul><ul><li>Oxygen </li></ul><ul><li>Pathogens </li></ul><ul><li>Vitamins </li></ul><ul><li>Viruses </li></ul><ul><li>Water </li></ul><ul><li>Fetal Transfer </li></ul><ul><li>Urea </li></ul><ul><li>Carbon dioxide </li></ul><ul><li>Other catabolites </li></ul>www.freelivedoctor.com
  15. 15. I. Physicochemical Properties of the Drug <ul><li>D. Molecular Size </li></ul><ul><ul><li>Depending on M.W. drugs cross the placenta readily (250-500), with difficulty (500-1000), or poorly (>1000). </li></ul></ul><ul><ul><li>The great majority of drugs have molecular weights between 100 and 500. </li></ul></ul><ul><ul><li>i.e. heparin vs warfarin. </li></ul></ul>www.freelivedoctor.com
  16. 16. I. Physicochemical Properties of the Drug <ul><li>E. Placental and Fetal Drug Metabolism </li></ul><ul><ul><li>40-60% of umbilical venous blood flow enters the fetal liver. </li></ul></ul><ul><ul><li>The fetal liver contains the adult complement of enzymes, however, at term, the activity of these enzymes is only about half those in the adult. </li></ul></ul><ul><ul><li>Liver enzymes in the fetus are poorly inducible. </li></ul></ul><ul><ul><li>Drug metabolites may be pharmacologically active and able to cause adverse effects in the fetus. </li></ul></ul><ul><ul><li>Several different aromatic oxidation reactions can occur in the placenta (e.g. hydroxylation, N- dealkylation, demethylation). </li></ul></ul>www.freelivedoctor.com
  17. 17. I. Physicochemical Properties of the Drug <ul><li>F. Placental Transport </li></ul><ul><li>1. Simple Diffusion. gases. </li></ul><ul><li>2. Facilitated Diffusion. glucose. </li></ul><ul><li>3. Active Transport. e.a.a. and water soluble vitamins. </li></ul><ul><li>4. Pinocytosis. Complex proteins, antibodies, small amounts of fat and viruses. </li></ul><ul><li>5. Leakage. Fetal cells exfoliate into the maternal circulation . </li></ul>www.freelivedoctor.com
  18. 18. II. Amount of Drug Reaching the Fetus <ul><li>Determined by the degree of plasma permeability to the drug and the drug’s physicochemical properties, as well as to the maternal absorption, distribution and biotransformation of the drug. </li></ul>www.freelivedoctor.com
  19. 19. III. Exposure Rate <ul><li>Determined by the degree of plasma permeability to the drug and the drug’s physicochemical properties, as well as to the fetal absorption, distribution and biotransformation of the drug. </li></ul>www.freelivedoctor.com
  20. 20. IV. Duration of Exposure <ul><li>Determined by the degree of placental permeability to the drug and the drug’s physicochemical properties. It will also depend on the maternal absorption, distribution, biotransformation and clearance of the drug as well as the fetal absorption, distribution, biotransformation and clearance of the drug . </li></ul><ul><li>Because the fetus clearance is via the kidney (urine) and the urine goes to the amniotic fluid, the fetus might take in the drug again. </li></ul>www.freelivedoctor.com
  21. 21. V. Tissue Distribution <ul><li>Drugs may be stored in tissues differently. </li></ul><ul><li>Drugs are removed from circulation and stored in bone, teeth, hair and adipose tissue. </li></ul><ul><li>Lipid soluble drugs are stored in adipose tissue, which increases during pregnancy, with a resulting prolonged effect of the drug (slow release). </li></ul>www.freelivedoctor.com
  22. 22. VI. Developmental Stage <ul><li>The fetus is most vulnerable during the first trimester. </li></ul><ul><ul><ul><li>From conception (0) to 14 days. </li></ul></ul></ul><ul><ul><ul><li> Little morphologic differentiation. </li></ul></ul></ul><ul><ul><ul><li>From 15 to 60 days after conception. </li></ul></ul></ul><ul><ul><ul><li>Time of organogenesis. Fetus is most vulnerable . </li></ul></ul></ul>www.freelivedoctor.com
  23. 23. Fetal Development CNS Heart Eyes Legs Arms 0 5 15 Teeth Palate Ex. genitalia Ear Full term www.freelivedoctor.com
  24. 24. Drug Affinity for Specific Tissues <ul><ul><li>Tetracycline </li></ul></ul><ul><ul><li>Warfarin </li></ul></ul><ul><ul><li>Aminoglycosides </li></ul></ul><ul><ul><li>Quinine </li></ul></ul><ul><ul><li>Chlorpromazine </li></ul></ul><ul><ul><li>Diethylstilbestrol </li></ul></ul><ul><ul><li>Corticosteroids </li></ul></ul><ul><ul><li>Phenytoin </li></ul></ul><ul><ul><li>Iodides </li></ul></ul><ul><ul><li>Propylthiouracil </li></ul></ul><ul><li>Teeth </li></ul><ul><li>Middle ear </li></ul><ul><li>Retina </li></ul><ul><li>Mullerian Duct </li></ul><ul><li>Vagina </li></ul><ul><li>Adrenal Gland </li></ul><ul><li>Thyroid Gland </li></ul>www.freelivedoctor.com
  25. 25. Factors Affecting Placental Transfer of Drugs <ul><li>Lipid solubility. </li></ul><ul><li>Nonionized substances. </li></ul><ul><li>Molecular weight < 600 </li></ul><ul><li>Low protein binding. </li></ul><ul><li>High maternal-fetal gradient. </li></ul><ul><li>Increased placental blood flow. </li></ul><ul><li>Increased fetal acidity. </li></ul><ul><li>Larger surface area. </li></ul><ul><li>Increased diffusion distance. </li></ul><ul><li>High molecular charge. </li></ul><ul><li>High molecular weight. </li></ul><ul><li>Drug bound to maternal RBCs or plasma protein. </li></ul><ul><li>Drug altered or bound by placental enzymes. </li></ul><ul><li>Decreased maternal blood flow. </li></ul><ul><li>Drugs highly metabolized by mother. </li></ul>www.freelivedoctor.com
  26. 26. Drug Therapy in Pregnancy <ul><li>PHARMACODYNAMICS </li></ul><ul><li>Factors Affecting Drug Actions in the Fetus: </li></ul><ul><ul><li>I. Maternal factors. </li></ul></ul><ul><ul><li>II. Fetal Therapy. </li></ul></ul><ul><ul><li>III. Drug Toxicity. </li></ul></ul><ul><ul><li>IV. Teratogenicity </li></ul></ul>www.freelivedoctor.com
  27. 27. I. Maternal Factors <ul><li>1) Reproductive tissues are altered by pregnancy (breast, uterus, etc). </li></ul><ul><li>2) Drug effects in other tissues are not significant. (except: for a decreased GI motility, delayed gastric emptying). </li></ul><ul><li>3) Other physiologic changes do occur => increased plasma volume, increased cardiac output, increased renal blood flow. </li></ul><ul><li>i.e. cardiac glycosides may be used for CHF due to increase work load. Insulin may be needed for pregnancy-induced diabetes. </li></ul>www.freelivedoctor.com
  28. 28. II. Fetal Therapy <ul><ul><li>Therapy directed to the fetus. </li></ul></ul><ul><ul><li>Corticosteroids. Stimulate fetal lung maturation when preterm birth is expected. </li></ul></ul><ul><ul><li>Phenobarbital. Given during the last trimester, close to term, induces fetal liver enzymes responsible for the glucoronidation of bilirubin, reducing the incidence of jaundice. </li></ul></ul><ul><ul><li>Antiarrhythmic drugs. For the treatment of fetal arrythmias. </li></ul></ul>www.freelivedoctor.com
  29. 29. III. Drug Toxicity <ul><ul><li>Many drugs of abuse cross the placenta. </li></ul></ul><ul><ul><li>Chronic use of opioids by the mother may produce dependence in the fetus and newborn and withdrawal . </li></ul></ul><ul><ul><li>Whatever is toxic to the mother will probably be toxic to the fetus. </li></ul></ul>www.freelivedoctor.com
  30. 30. IV. Teratogenicity <ul><ul><li>A. Teratogen </li></ul></ul><ul><ul><li>B. Teratogenic Mechanisms </li></ul></ul><ul><ul><li>C. Teratogenic Risk </li></ul></ul>www.freelivedoctor.com
  31. 31. IV. Teratogenicity <ul><ul><li>I. Teratogen. Substance capable of causing abnormal development or function by interfering with fetal development. </li></ul></ul><ul><ul><ul><ul><li>A single intrauterine exposure to the drug can affect the fetal structures undergoing rapid development at the time of exposure. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Characteristic set of malformations. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Exert its effects at a particular time in fetal development. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Show a dose-dependent incidence. </li></ul></ul></ul></ul><ul><ul><li>i.e. alcohol (FAS), Thalidomide (phocomelia), DES (uterine cancer), valproic acid (spina bifida). </li></ul></ul>www.freelivedoctor.com
  32. 32. Drugs that cause severe adverse effects <ul><li>ACE Inhibitors </li></ul><ul><li>Aminopterin </li></ul><ul><li>Amphetamines </li></ul><ul><li>Androgens </li></ul><ul><li>TCAs </li></ul><ul><li>BARBs </li></ul><ul><li>Busulfan </li></ul><ul><li>Carbamazepine </li></ul><ul><li>Chlorpropamide </li></ul><ul><li>Clomipramine </li></ul><ul><li>Cocaine </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Cytarabine </li></ul><ul><li>Diazepam </li></ul><ul><li>DES </li></ul><ul><li>Ethanol </li></ul><ul><li>Etretinate </li></ul><ul><li>Heroin </li></ul><ul><li>Iodide </li></ul><ul><li>Isotretinoin </li></ul><ul><li>Lithium </li></ul><ul><li>Methadone </li></ul><ul><li>Methotrexate </li></ul><ul><li>Methylthiouracil </li></ul><ul><li>Metronidazole </li></ul><ul><li>Organic solvents </li></ul>Misoprostol Penicillamine Phencyclidine Phenytoin Propylthiouracil Streptoycin Tamoxifen Tetracycline Thalidomide Trimethadione Valproic acid Warfarin www.freelivedoctor.com
  33. 33. IV. Teratogenicity <ul><ul><li>B. Teratogenic Mechanisms : </li></ul></ul><ul><ul><ul><li>1) Effects on maternal tissues. </li></ul></ul></ul><ul><ul><ul><li>2) Delivery of oxygen and nutrients. </li></ul></ul></ul><ul><ul><ul><li>3) Alterations during differentiation. </li></ul></ul></ul><ul><ul><ul><li>4) Deficiencies. </li></ul></ul></ul>www.freelivedoctor.com
  34. 34. IV. Teratogenicity <ul><li>1) Effects on maternal tissues. </li></ul><ul><ul><li>Drugs may have a direct effect on maternal tissues with secondary or indirect effects in the fetus. </li></ul></ul><ul><ul><li>e.g. Cocaine increases the risk for spontaneous abortions, placenta previa and permature labor; neonatal cerebral infarction, abnormal development and decrease school performance. </li></ul></ul>www.freelivedoctor.com
  35. 35. IV. Teratogenicity <ul><li>2) Delivery of oxygen. </li></ul><ul><ul><ul><li>Interference of oxygen delivery to the fetus may cause ischemia to tissues specially to brain, and cause severe damage or even death. </li></ul></ul></ul>www.freelivedoctor.com
  36. 36. IV. Teratogenicity <ul><li>3) Food and Nutrient alterations during differentiation. </li></ul><ul><ul><ul><li>Interference with nutrient delivery may cause anemia and poor growth. </li></ul></ul></ul><ul><ul><ul><li>Alterations of certain factors such as vitamins or minerals may be teratogenic. </li></ul></ul></ul><ul><ul><li>e.g. Vitamin A (Retinol) has important differentiation-directing actions in normal tissues. Excessive amounts may cause birth defects, bone abnormalities and liver damage. </li></ul></ul><ul><ul><li>Excess niacin may cause ocular abnormalities. </li></ul></ul>www.freelivedoctor.com
  37. 37. IV. Teratogenicity <ul><li>4) Deficiencies. </li></ul><ul><ul><li>Alterations of certain factors such as vitamins or minerals may be teratogenic. </li></ul></ul><ul><ul><li>e.g. Folic acid causes neural tube defects, supplementation reduces the incidence of spina bifida. </li></ul></ul>www.freelivedoctor.com
  38. 38. IV. Teratogenicity <ul><ul><li>C. Teratogenic Risk </li></ul></ul><ul><ul><li>It is recommended that all pregnant women be counseled with regard to taking medications during pregnancy. </li></ul></ul><ul><ul><li>In reality, the risk of a neonatal abnormality in the absence of any known teratogen is less than 3%. </li></ul></ul><ul><ul><li>Up till know about 30 compounds have been identified to be teratogenic. </li></ul></ul>www.freelivedoctor.com
  39. 39. Drug Therapy in Infants <ul><li>PHARMACODYNAMICS </li></ul><ul><li>Factors Affecting Drug Effects on the Infant: </li></ul><ul><ul><ul><li>I. Drug Absorption </li></ul></ul></ul><ul><ul><ul><li>II. Drug Distribution </li></ul></ul></ul><ul><ul><ul><li>III. Drug Metabolism </li></ul></ul></ul><ul><ul><ul><li>IV. Drug Excretion </li></ul></ul></ul>www.freelivedoctor.com
  40. 40. Drug Therapy in Infants <ul><li>I. Drug Absorption </li></ul><ul><li>Absorption in infants and children follows the same rules as in adults. </li></ul><ul><li>Factors affecting absorption are determined by the physiologic status of the infant or child and are influenced by: </li></ul><ul><ul><li>1.) Blood flow at the site of administration. </li></ul></ul><ul><ul><li>2.) Gastrointestinal function. </li></ul></ul>www.freelivedoctor.com
  41. 41. Drug Therapy in Infants <ul><li>Drug Absorption in </li></ul><ul><li>Drug </li></ul><ul><li>Acetaminophen </li></ul><ul><li>Ampicillin </li></ul><ul><li>Diazepam </li></ul><ul><li>Digoxin </li></ul><ul><li>Penicillin G </li></ul><ul><li>Phenobarbital </li></ul><ul><li>Phenytoin </li></ul><ul><li>Sulfonamides </li></ul><ul><li>the neonate compared to adults. </li></ul><ul><li>Oral Absorption </li></ul><ul><li>Decreased </li></ul><ul><li>Increased </li></ul><ul><li>Normal </li></ul><ul><li>Normal </li></ul><ul><li>Increased </li></ul><ul><li>Decreased </li></ul><ul><li>Decreased </li></ul><ul><li>Normal </li></ul>www.freelivedoctor.com
  42. 42. Drug Therapy in Infants <ul><li>1.) Blood flow at the site of administration. </li></ul><ul><ul><li>- Physiological conditions that might affect blood flow are: cardiovascular shock, vasoconstriction (sympathomimetic agents), and heart failure. </li></ul></ul><ul><ul><li>- Diminished muscle mass in i/ch may reduce blood flow causing irregular and unpredicatble absorption. Drug will concentrate in the muscle and if perfusion suddenly increases, drug may reach toxic concentrations. </li></ul></ul><ul><ul><li>e.g. cardiac glycosides, aminoglycoside antibiotics, and anticonvulsants. </li></ul></ul><ul><ul><li>2.) Gastrointestinal function. </li></ul></ul>www.freelivedoctor.com
  43. 43. Drug Therapy in Infants <ul><li>2.) Gastrointestinal function. </li></ul><ul><li>Significant changes occur in the neonate shortly after birth. </li></ul><ul><li>Gastric acid secretion commences soon after birth and increases gradually over several hours. In preterm infants it appears slowly. Drugs affected by gastric pH should not be administered orally. </li></ul><ul><li>Gastric emptying is prolonged in the first day of life. Thus, drugs absorbed through GI may be more completely absorbed than anticipated. </li></ul><ul><li>Peristalsis in the neonate is slow. If drugs are absorbed in the small intestine, their effect may be delayed. Diarrhea causes decrease absorption in small intestine. </li></ul>www.freelivedoctor.com
  44. 44. Drug Therapy in Infants <ul><li>II. Drug Distribution </li></ul><ul><li>As body composition changes with development so does the distribution volume of drugs. </li></ul><ul><li>In the neonate, 70-75% of body weight is water vs 85% in preterm vs 50-60% in the adult. </li></ul><ul><li>Most neonates will experience diuresis in the first 24-48hrs of life. </li></ul><ul><li>In neonate 40% of body weight is extracellular water vs 20% in the adult. </li></ul><ul><li>In the neonate total body fat is 15% vs 1% in preterm. </li></ul>www.freelivedoctor.com
  45. 45. Drug Therapy in Infants <ul><li>II. Drug Distribution </li></ul><ul><li>Binding to Plasma protein </li></ul><ul><li>Protein binding of drugs is reduced in the neonate. Therefore, concentration of free drug in plasma is increased => increased effect or increase toxicity. </li></ul><ul><li>Drugs (e.g. sulfonamide antibiotics) that displace bilirubin from albumin may cause kernicterus. Conversely, bilirubin may also displace protein-bound drugs (e.g. phenytoin). </li></ul>www.freelivedoctor.com
  46. 46. Drug Therapy in Infants <ul><li>III. Drug Metabolism </li></ul><ul><li>Metabolism of most drugs occurs in the liver. </li></ul><ul><li>The metabolizing activity of cytochrome P450-dependent mixed-function oxidases is reduced in neonates (50-70% of adult values). </li></ul><ul><li>Glucoronide formation doesn’t occur until the 3th -4rd years of life. Thus, in the neonate, drugs have slow clearance rates and prolonged half-lives. </li></ul><ul><li>If the mother was taking phenobarbital, neonatal liver enzymes could have been induced. The ability of the neonate to metabolize certain drugs would be greater than expected and the effect could be less. </li></ul>www.freelivedoctor.com
  47. 47. Biotransformation of Benzodiazepines From Katzung, 1998 www.freelivedoctor.com
  48. 48. Drug Therapy in Infants <ul><li>IV. Drug Excretion </li></ul><ul><li>Glomerular filtration is much lower (30-40% of adult) in neonates for the first few days of life. Within a week glomerular filtration and plasma flow increase by 50% and reach adult values within 6-12 months. Drugs that depend on renal flow are eliminated very slowly in the first few weeks of life (penicilins, aminoglycoside antibiotics, digoxin) </li></ul><ul><ul><li>Ampicillin </li></ul></ul><ul><ul><li>< 7 days old=> 50-100 mg/Kg/d , 2d at 12 hr intervals. </li></ul></ul><ul><ul><li>> 7 days old => 100-200 mg/Kg/d, 3d at 8 hr intervals. </li></ul></ul>www.freelivedoctor.com
  49. 49. Drug Therapy in Infants <ul><li>Dosage Forms and Compliance: </li></ul><ul><li>To ease administration and compliance, drug manufacturers prepare drugs as: </li></ul><ul><li>Elixirs. Alcoholic solutions in which the drug molecules are dissolved and evenly distributed. </li></ul><ul><li>Suspensions. Contain undissolved particles of drug which must be distributed throughout the vehicle by shaking to prevent uneven drug dispensing. </li></ul>www.freelivedoctor.com
  50. 50. Drug Therapy in Infants <ul><li>Compliance may be difficult to achieve in pediatric medicine and may prove a challenge when taking into account: </li></ul><ul><ul><ul><li>measuring errors </li></ul></ul></ul><ul><ul><ul><li>spills </li></ul></ul></ul><ul><ul><ul><li>spitting </li></ul></ul></ul><ul><li>A calibrated medicine spoon should be recommended. </li></ul><ul><li>Parents should be told to repeat dosage or not after spitting or whether to wake up the child every 6 hr dose day or night. Possible drug-drug interactions with ODC medications should be discussed. </li></ul>www.freelivedoctor.com
  51. 51. Drug Therapy in Infants <ul><li>NO ASSUMPTIONS SHOULD BE MADE ABOUT WHAT THE PARENT MAY OR MAY NOT DO. </li></ul>www.freelivedoctor.com
  52. 52. Drug Therapy in Infants <ul><li>Drugs Contraindicated </li></ul><ul><li>Amphetamine </li></ul><ul><li>Bromocryptine </li></ul><ul><li>Cocaine </li></ul><ul><li>Cyclophosphamide </li></ul><ul><li>Cyclosporine </li></ul><ul><li>Doxorubicin </li></ul><ul><li>during Lactation: </li></ul><ul><li>Ergotamine </li></ul><ul><li>Heroin </li></ul><ul><li>Lithium </li></ul><ul><li>Marijuana </li></ul><ul><li>Methotrexate </li></ul><ul><li>Nicotine </li></ul><ul><li>Phenindione </li></ul>www.freelivedoctor.com
  53. 53. FDA Drug Categories <ul><li>Category A . Controlled Studies have not demonstrated fetal risk. </li></ul><ul><li>Category B . Studies in animals have not demonstrated fetal risk. </li></ul><ul><li>Category C . Studies in women or animals are not available. </li></ul><ul><li>Category D . There is positive evidence of human risk. However, the benefits of use in pregnancy may be acceptable in spite of this risk. </li></ul><ul><li>Category X . Studies or experience in humans or animals has demonstrated fetal risk. The risk far outweighs any potential benefit. The drug is contraindicated in pregnant women or women who may become pregnant. </li></ul>www.freelivedoctor.com

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